WHO/HTM/TB/2015.

28

Active tuberculosis drug-safety

monitoring and management (aDSM)

Framework for implementation

November 2015

Active tuberculosis drug-safety monitoring and

management (aDSM)
Background
Health programmes that systematically monitor patient safety are in a better
position to prevent and manage adverse drug reactions (ADRs), improve healthrelated quality of life, and improve treatment outcomes. Likewise, national
tuberculosis (TB) programmes that actively pursue drug-safety monitoring and
management are better prepared to introduce new TB drugs and novel
regimens.
The prospects of new anti-TB drugs and use of novel regimens led WHO to
release its first implementation manual for pharmacovigilance of anti-TB drugs in
2012 (1). Later in 2012, WHO provided interim advice that the use of shorter
regimens for multidrug-resistant TB (MDR-TB) be accompanied by the collection
of drug-safety data within a framework of observational research (2). In 2013
and 2014, the WHO interim policies on bedaquiline and delamanid recommended
active pharmacovigilance as one of the five conditions to be met when these
drugs are used to treat MDR-TB patients (3),(4).
National TB programmes (NTPs) and other stakeholders are now starting to
introduce new anti-TB drugs and novel MDR-TB regimens according to WHO
recommendations. A number of programmes managing MDR-TB patients have
also introduced active pharmacovigilance to monitor drug-safety and to take
early action to avert treatment interruption and other unfavourable patient
outcomes (5),(6),(7).
The application of pharmacovigilance methods such as cohort event monitoring
described in the 2012 WHO Handbook which were largely based on experience
with the use of drugs for malaria, HIV and non-communicable diseases led to
practical questions related to the implementation of drug-safety monitoring
alongside other components of programmatic management of drug-resistant TB
(PMDT).
The lack of familiarity of many TB practitioners with the principles of drug-safety
monitoring, and the limited capacity of national drug-safety authorities in some
countries to provide the necessary support, have resulted in requests for more
explicit guidance. A recent survey conducted by Mdecins Sans Frontires (MSF)
and the Stop TB Partnerships Global Drug Facility (GDF) in the 27 high MDR-TB
burden countries showed concerns about ADRs as one of the main barriers
identified for the introduction of bedaquiline and delamanid (MSF/GDF,
unpublished information).
Several stakeholders have also expressed concern that the introduction of new
anti-TB drugs may be slowed down or even prevented due to a lack of capacity
by countries to mount conventional active pharmacovigilance. The WHO Global

TB Programme (WHO/GTB) therefore convened key technical and funding

agencies to a meeting in Geneva, Switzerland on 28-29 July 2015 to discuss
essential requirements for the implementation of active pharmacovigilance and
proper management of ADRs when introducing new anti-TB medicines or novel
MDR-TB regimens. This document reflects the consensus achieved during this
meeting and in subsequent discussions also involving NTP managers of selected
countries and the WHO Essential Medicines and Health Products Department
(see list of contributors in Annex 1).
Other WHO documents particularly the Companion Handbook to the WHO
guidelines for the programmatic management of drug-resistant TB (the PMDT
Handbook) (8), the Policy Implementation Package for new TB drug introduction
(9), and the current WHO/GTB website on TB drug safety and the associated
frequently asked questions (10) - will also be updated accordingly.

Introducing active TB drug-safety monitoring and applicable

terminology
The concept of cohort event monitoring and other conventional terminology of
pharmacovigilance are foreign to many TB practitioners and recent
recommendations for their introduction in PMDT programmes have created some
confusion. Moreover, not all countries are at equal levels of maturity in
implementing general pharmacovigilance activities (11), (12).
This document therefore outlines the agreed essential requirements for active
drug-safety monitoring and management in patients on treatment for drugresistant TB.1 It proposes key terms that were adapted to the specific context of
active TB drug-safety monitoring (see Annex 2 for a glossary of the main terms).
This adaptation should help the TB community to speak the same language while
implementing the required drug-safety activities.
The term active TB drug-safety monitoring and management (abbreviated as
aDSM) defines the active and systematic clinical and laboratory assessment of
patients while on treatment. aDSM applies to patients on treatment with i) new
anti-TB drugs; ii) novel MDR-TB regimens; or iii) XDR-TB regimens, in order to
detect, manage and report suspected or confirmed drug toxicities.
The recording and reporting activities of aDSM primarily target the serious
adverse events (SAEs) as a core requirement. PMDT sites with additional
resources may also monitor other AEs which are of clinical significance or of
special interest to the PMDT programme, as part of an extended aDSM approach
(see below and also Annexes 2 and 3).
1

While drug-safety issues are also relevant in the management of drug susceptible TB, the safety profiles of
first-line TB drugs are well-described and not considered necessary to be covered by active drug-safety
monitoring.

The appropriate and timely management of all AEs and ADRs is an integral
component of aDSM and patient care. Details on the management of AEs and
ADRs are included elsewhere (see Chapter 11 of the PMDT Handbook (8)) and
are not repeated in this document.
Setting up aDSM for patients on treatment for drug-resistant TB implies
additional responsibilities and resource needs. In contrast to the surveillance of
drug-resistance and treatment outcomes, the active systematic monitoring of
the occurrence of SAEs is relatively new to TB programmes. Implementation,
management and supervision necessary for aDSM should be systematically built
into the PMDT component of the TB programme and be conducted in step with
other activities related to patient care and monitoring.
Close coordination of aDSM activities with the main pharmacovigilance structures
at country level is essential to avoid overlap and duplication. Even countries with
mature conventional pharmacovigilance systems may need to establish an aDSM
component within PMDT programmes to ensure that patients are adequately
monitored and all SAEs (at least) are detected, managed, and reported rapidly.

Patients to whom aDSM applies

MDR-TB and XDR-TB patients treated with new medicines, such as

bedaquiline or delamanid;

MDR-TB patients enrolled on treatment with novel regimens, such as

those much shorter than currently recommended by WHO;

All other XDR-TB patients on second-line treatment (as these regimens

often include multiple repurposed drugs),

Once these groups of patients are covered, aDSM can be extended to other
patients on treatment with conventional MDR-TB regimens, depending on the
resources available.

Objectives of aDSM
aDSM is not expected to meet all the criteria for conventional cohort event
monitoring. The overall objectives of aDSM are to reduce risks from drug-related
harms in patients on second-line treatment for drug-resistant TB and to
generate standardised aDSM data to inform future policy updates on the use of
such medicines.
To achieve these objectives, aDSM includes three essential activities:

Patients targeted for aDSM should undergo active and systematic clinical and
laboratory assessment during treatment to detect drug toxicity and AEs.
Proposed schedules have been developed for use in patients on shorter
regimens or on new medications (5),(8);

All AEs detected should be managed in a timely fashion in order to deliver the
best possible patient care. Management of AEs is beyond the scope of this
note and further details are provided in other implementation documents
such as the PMDT Handbook (8);

Standardised data should be systematically collected and reported for any

SAE detected2: these will eventually be used to characterize the types of
SAEs, assess the safety of the treatment and to inform future policy on the
use of these medicines.

All SAEs detected should be reported to the national authority responsible for
pharmacovigilance according to individual country requirements (including time
limits for reporting) and should be regularly assessed for causality.
WHO will work with partners to establish a global database for aDSM to enhance
the detection of new signals and to inform future updates of global policies on
the use of anti-TB drugs and novel regimens. This is distinct from existing
mechanisms for the global coordination of spontaneous reports from national
pharmacovigilance systems.

Three levels of monitoring in aDSM

1. Core package: requiring monitoring for and reporting of all SAEs
2. Intermediate package: includes SAEs as well as AEs of special interest3
3. Advanced package: includes all AEs of clinical significanc3
All PMDT sites treating eligible patients with new anti-TB drugs, novel MDR-TB
regimens or for XDR-TB require the Core package. These treatment centres
should, as a minimum, also be taking part in spontaneous reporting of ADRs as
required by local regulations. Expansion of aDSM should be implemented in a
phased approach as and when resources permit.

Implementing aDSM
Based upon the experience of the successful implementation of other care and
monitoring components of PMDT programmes, eight key steps have been
identified for programmes to follow when introducing aDSM (Figure 1).
2

Countries and stakeholders may also monitor other AEs of special interest or clinical significance (see next
section).
3
See Annexes 2 and 3 for definitions of these terms.

Figure 1. Key steps to implementing aDSM

Create a national coordinating mechanism for aDSM

Develop a plan for aDSM
Define management and supervision roles and responsibilities
Create standard data collection materials
Train staff on the collection of data
Define schedules and routes for data collection and reporting
Consolidate aDSM data electronically
Develop (or use existing) capacity for signal detection and causality
assessment
Ideally, all eight steps should be in place before patients are enrolled on
treatment with new drugs, novel MDR-TB regimens or XDR-TB treatment. As this
may not always be feasible, two steps are essential ahead of any patient
enrolment, i.e.
i)
ii)

creating standard data collection materials; and

training staff on the collection of data

By having these minimum conditions in place there is less likelihood that data
are lost and that opportunities to manage AEs and ADRs are missed.
The responsibility for the coordination of aDSM at national level should be
assigned to an existing TB expert body, such as the MDR-TB committee (or
consilium) or the technical working group on new drugs. These committees
should primarily have scientific and clinical expertise for MDR-TB care and drug
safety monitoring but may also include expertise important for coordination and
communication (e.g. funding, advocacy, patient representation). Until such
group is tasked with this role the NTP needs to assign someone to coordinate the
necessary aDSM activities and ensure that the two key steps mentioned above
are in place prior to patient enrolment.
The aDSM plan should define clearly the activities and the standard operating
procedures, including the plan for data collection, reporting of indicators,
analyses and communication. The final document should be incorporated within
6

the national TB or PMDT guidelines. Local and/or international experts in drugsafety as well as the national pharmacovigilance centre should be engaged.
While some of the data collection tools for aDSM are separate from those used
for routine PMDT programme monitoring, the process should be integrated with
the other cohort-based monitoring for bacteriological response and outcomes
that has been a standard feature of the PMDT component of TB programmes for
several years (see Chapter 2 and Annexes of (8)). WHO is working closely with
NTPs and partners towards further integration of aDSM within routine PMDT
programme monitoring.
In the Core Package of aDSM, clinical and laboratory test records at baseline
(treatment initiation) and during regular review (e.g. monthly intervals) should
be integrated into an expanded version of the programmatic MDR-TB (Secondline TB) Treatment Card (see Annex 4 for an example). The treatment initiation
form should be completed before the start of treatment (to document any
abnormality which could later be confused with a drug-related SAE) and the
review form should be completed at scheduled encounters with the patient. In
addition, information on SAEs occurring in-between visits should also be
captured using the same forms.
A standard form (in paper or electronic format) to alert the programme when
any SAE occur will need to be developed (see Annex 5 for an example). Its
content could be similar to that used by the national pharmacovigilance centre
for spontaneous reporting.
For the Intermediate and Advanced Packages of aDSM, additional data collection
forms will have to be used to record data at baseline and during regular followup. Templates of such forms have been developed and can be adapted to
individual programme needs (13).
Staff at the different levels of health services should be informed and trained on
the use of the new anti-TB drugs or novel regimens ahead of any patient
enrolment. This training would need to include instruction on the completion of
the aDSM forms. It is important that this activity is completed ahead of any
patient enrolment to ensure timely identification of adverse events which need
to be managed as well as proper and complete collection of information.
All adverse events detected during routine clinical patient care should lead to an
appropriate and timely management response in order to limit potential harms
to the patient. In terms of monitoring, the minimum requirement for aDSM is
that all SAEs be registered and reported, regardless of their severity or whether
they are known to have been caused by any of medicines to which the patient is
exposed.
Some centres with sufficient resources may be designated as sentinel sites and
undertake additional monitoring to that required by the Core Package of aDSM,
7

such as the reporting of AEs of special interest or AEs of clinical significance (see
above). In addition, in many countries the reporting of ADRs to the national
pharmacovigilance centre is mandated by law. As for all other public and private
health services, TB practitioners should comply with the national legal
requirements for such reporting.
The creation of an electronic database - or preferably the adaptation of an
existing TB patient database to accommodate the additional data fields required
- is an important step in aDSM implementation. It will ensure the standardisation
and safekeeping of the data. If data are collected on paper forms these need to
be entered regularly into the electronic database. The management of data in
electronic format is indispensable and will facilitate the sharing of data,
generation of indicators and analysis.
Measures should be taken to avoid duplication of work by revising existing
databases, ensuring interoperability of data management systems, consulting
with local pharmacovigilance authorities and granting access rights to users for
different data as needed (see Figure 2). The roles and responsibilities for data
management and analysis should be specified in the aDSM plan to avoid the
creation of parallel systems of ADR reporting and make use of the best possible
expertise and capacity in the country on drug safety.
The ultimate purpose of systematic data collection within aDSM is to enable
causality assessment for serious adverse events, determine their frequency
(rates) and to detect signals. Physicians skilled in MDR-TB management already
attempt to assess relationships between drugs and ADRs and take appropriate
clinical action. Nevertheless, formal causality assessment is a separate process
that requires involvement of other experts. In a number of countries, the
capacity of the national pharmacovigilance centres to conduct formal causality
assessment is very limited but where such capacity exists it should be availed of.
National TB programme staff should acquire the skills necessary to undertake
the essential activities related to aDSM. This is a long-term goal but needs to be
started as part of the plan to introduce new anti-TB drugs and novel MDR-TB
regimens. Local and/or international expertise in causality assessment needs to
be sought by the programme to carry out such capacity building. WHO is also
working with partners to accelerate such capacity building efforts.

Figure 2. Generic model of how aDSM is positioned within drug-safety structures at the national level
aDSM adapted to the local situation to avoid the creation of parallel systems of reporting

National TB Programme
PATIENT SAFETY
MANAGEMENT & CARE

DRUG SAFETY
MONITORING

(PMDT component)

(aDSM component)

Delivery of
treatment

Management of
adverse reactions

Cohort-based follow-up of
patients with
questionnaires to elicit
symptoms; and
routine tests for TB
drug safety monitoring
Recording of at least all SAEs
in a National aDSM database
(regularly transferred into
global database)
Signal detection / causality
assessment by NTP (if
capacity is limited at NPV)

Inform update of
treatment policy and
patient care practice
(as per PMDT guidance)

National Pharmacovigilance System

Link for reporting,
causality assessment,
signal detection, etc.

Reporting as
required by local
regulations

Further analysis for signal

detection/causality
assessment
&
Communication

Support of to
signal detection &
causality assessment

New
Evidence

Inform updates of
country and global drug
safety profile

Support to the implementation of aDSM

The implementation of aDSM at TB programme level will be greatly facilitated by
familiarity with the concept of cohort-based follow-up of patients, which is the
basis of monitoring and evaluation of TB and MDR-TB treatment programmes. To
date a number of countries have already successfully integrated clinical and
laboratory testing schedules for active drug-safety monitoring within the TB
patient cohort framework which they use to monitor treatment response and
outcomes (5),(6). The testing schedules used in these projects have largely
followed those generally recommended when second-line TB drugs are used (8).
Experience from observational studies of shorter regimens for MDR-TB has
shown that active drug-safety monitoring can be feasibly implemented within
programmes if dedicated funding is provided. Most of the additional resources
are needed to undertake clinical testing (e.g. electrocardiography, audiometry)
and laboratory analyses, as well as undertaking the added work to collect the
safety data.
It is envisaged that once the right skills have been acquired, and links
established with appropriate experts in drug-safety, causality assessment and
signal detection could be organised within the PMDT programme with
appropriate capacity building and support from drug-safety experts (if such
capacity is missing at the national pharmacovigilance system). More work is
needed to quantify the costs of aDSM and these will eventually be reflected in
tools to help users with budgeting.
While clinicians treating patients with second-line anti-TB drugs are usually
familiar with clinical monitoring for adverse events, this knowledge may not be
shared by many other health care workers within the programme. The
monitoring component of aDSM is also likely to be novel to many health care
workers. WHO/GTB and technical partners will be supporting national TB
programmes to build such capacity and to integrate aDSM into routine PMDT
monitoring. A training plan and resources for building capacity will be created by
early 2016.
Likewise, the creation of a global central database to pool anti-TB drug-safety
data collected through aDSM projects in different countries is envisaged from
early 2016. This could increase the likelihood of detecting rare adverse events.
Separate guidance will be prepared to guide national programmes on how to
submit their data to the global database.

10

Summary aDSM in brief

Active TB drug safety monitoring and management (aDSM for short)
refers to the active and systematic clinical and laboratory assessment of patients
on treatment with i) new anti-TB drugs; ii) novel MDR-TB regimens; or iii) XDRTB regimens, to detect, manage and report suspected or confirmed drug
toxicities.
While all detected adverse events (AEs) need to be managed clinically, the
Core Package of aDSM requires the reporting of serious AEs (SAEs) only. PMDT
sites with additional resources may also monitor other AEs which are of clinical
significance or of special interest to the programme, as part of comprehensive
aDSM. aDSM may also be expanded in a phased approach to eventually cover TB
patients on treatment with any second-line drugs should programmes wish to do
so.
aDSM is intended to be an integral component of PMDT programmes. Its
rationale is based on recent developments in MDR-TB treatment, particularly the
approval for use of new medicines ahead of the completion of Phase 3 trials,
increased use of repurposed drugs for XDR-TB treatment and the development
of novel second-line anti-TB regimens. Such approaches need careful monitoring
for drug-related harms, some of which may as yet not be described.
aDSM is not aimed at replacing or duplicating efforts of national
pharmacovigilance units but to complement current capacities and address
barriers to undertake active pharmacovigilance within the context of TB care. In
addition to drug-safety monitoring, aDSM also incorporates a component which
promotes the clinical management of all ADRs and AEs regardless of
seriousness. This monitoring and management needs to be adapted to the
realities of TB programmes which are often under-resourced.
In order for national programmes to undertake aDSM effectively, a series
of activities need to be coordinated to ensure that the right expertise is
developed through interaction with local and external drug-safety experts, and
that sufficient funds are made available to ensure that the clinical monitoring
activities are performed, the data collected, reported and analysed, and
decisions made based on the new knowledge gained.

11

Annex 1. List of Contributors

Amy Bloom
United States Agency for International Development
Philipp du Cros
Mdecins Sans Frontires
Janet Ginnard
UNITAID
Alex Golubkov
United States Agency for International Development
Brian Kaiser
UNITAID
Antonia Kwiecien
Management Sciences for Health
Nguyen Viet Nhung,
National TB Programme, Viet Nam
Nguyen Thi Thuy
National TB Programme, Viet Nam
Alberto Piubello
Action Damien
Ana Scardigli
The Global Fund to Fight AIDS, Tuberculosis and Malaria
Alena Skrahina
National TB Programme, Belarus
Arnaud Trbucq
UNION
Susan van den Hof
KNCV Tuberculosis Foundation
Francis Varaine
Mdecins Sans Frontires (representing the EndTB project)
WHO/HQ Secretariat
Dennis Falzon (GTB)
Christine Halleux (TDR)
Ernesto Jaramillo (GTB)
Christian Lienhardt (GTB)
Fuad Mirzayev (GTB)
Linh Nguyen (GTB)
Piero Olliaro (TDR)
Mario Raviglione (GTB)
Shanthi Pal (EMP)
Lembit Rago (EMP)
Karin Weyer (GTB)

12

Annex 2. Glossary of terms for active tuberculosis drug-safety monitoring

and management (aDSM)
In addition to the new terms (marked with an asterisk), the definition of other terms
may have been modified slightly from those in general usage to apply better to the
context of national tuberculosis programmes.

active TB drug-safety monitoring and management (aDSM)* is the active

and systematic clinical and laboratory assessment of patients on treatment with
i) new anti-TB drugs; ii) novel MDR-TB regimens; or iii) XDR-TB regimens; to
detect, manage and report suspected or confirmed drug toxicities. While all
detected adverse events (AEs) need to be managed, the core package of aDSM
requires the reporting of serious AEs only. M/XDR-TB treatment sites with
additional resources may also monitor other AEs which are of clinical significance
or of special interest to the programme, as part of comprehensive aDSM.
adverse drug reaction (ADR) is a response to a TB medicine which is noxious
and unintended, and which occurs at doses normally used in humans.
adverse event (AE) is any untoward medical occurrence that may present in a
TB patient during treatment with a pharmaceutical product, but which does not
necessarily have a causal relationship with this treatment.
serious adverse event (SAE) is an adverse event which either leads to death
or a life-threatening experience; to hospitalization or prolongation of
hospitalization; to persistent or significant disability; or to a congenital anomaly.
Serious events which do not result immediately in one of these outcomes but
which might require an intervention to prevent it from happening are included
(14). SAEs may require a drastic intervention such as termination of the drug
suspected of having caused the event.
adverse event of clinical significance* is an adverse event which is either (i)
serious, (ii) of special interest, (iii) leads to a discontinuation or change in the
treatment, or (iv) is judged as otherwise clinically significant by the clinician (see
Annex 3). The centres which offer the advanced package of aDSM will include all
adverse events of clinical significance in their reporting.
adverse event of special interest* is an adverse event documented to have
occurred during clinical trials and for which the monitoring programme is
specifically sensitized to report regardless of its seriousness, severity or causal
relationship to the TB treatment (see Annex 3). The centres which offer the
intermediate and advanced packages of aDSM will include all adverse events of
special interest in their reporting.
adverse event leading to treatment discontinuation or change in drug
dosage*, is an adverse event which leads a clinician to stop, interrupt
temporarily or change the dosage of one or more drugs, regardless of its
seriousness, severity, or causal relationship to the TB treatment.
causal relationship is a relationship between an exposure (A) and an event (B)
in which A precedes and causes B. This may refer to the causal association
between an exposure to a TB medicine and the occurrence of an adverse
reaction.

13

causality assessment is the evaluation of the likelihood that a TB medicine

was the causative agent of an observed adverse reaction.
drug-safety profile* is a description of the benefits, risks and toxicity of a
given TB drug or regimen, specifying any known or likely safety concerns,
contraindications, cautions, preventive measures and other features which the
user should be aware of to protect the health of a TB patient.
sentinel sites* are centres which, in addition to the core package of aDSM,
also undertake intermediate or advanced levels of drug-safety monitoring.
signal is reported information on a possible causal relationship between an
adverse event and a TB medicine, the relationship being unknown or
incompletely documented previously or representing a new aspect of a known
association. The information may arise from one or multiple sources that are
judged to be of sufficient likelihood to justify verification(15).

14

Annex 3. Adverse events of clinical significance or special interest for aDSM

See Annex 2 for the definition of types of adverse events mentioned on this page

1) All serious adverse events (SAEs)

2) All adverse events of special interest (suggested list)4:

Peripheral neuropathy (paraesthesia),

Psychiatric disorders and central nervous system toxicity (e.g.
depression, psychosis, suicidal intention, seizures)
Optic nerve disorder (optic neuritis) or retinopathy,
Ototoxicity (hearing impairment, hearing loss).
Myelosuppression (manifested as anaemia, thrombocytopenia,
neutropenia or leukopenia),
Prolonged QT interval (Fridericia correction; see (8))
Lactic acidosis
Hepatitis (defined as increases in alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) 5x the upper limit of normal
(ULN), or increases in ALT or AST 3x ULN with clinical
manifestations, or increases in ALT or AST 3x ULN with concomitant
increase in bilirubin 1.5 x ULN)
Hypothyroidism,
Hypokalaemia,
Pancreatitis
Phospholipidosis
Acute kidney injury (acute renal failure)

3) Adverse events leading to treatment discontinuation or change in drug dosage

4) Adverse events not listed above but judged as otherwise clinically significant
by the clinician

Adapted from (16)

The list shown here is provisional and may be modified according to the regimen composition or

the patient cohort.

15

Annex 4
Active tuberculosis drug-safety monitoring and management (aDSM)

CLINICAL AND LABORATORY TESTING SCHEDULE FOR aDSM

to be adapted to the local treatment regimen and national policy (ref.1)
M0

M1

M2

M3

M4

M5

M6

M7

M8

M9

M10

M11

M12

M13

M14

M15

M16

M17

M18

M19

M20

M21

M22

M23

Date
Clinical screen
Visual acuity
Simple hearing test
Audiogram
Neuro & psychiatric
investigations
Serum creatinine
ALT (SGPT)
AST (SGOT)
Bilirubin
Alkaline phosphatase
GT
ECG
Lipase
Amylase
Potassium
Magnesium
Calcium
Albumin
Complete Blood Count
Blood glucose
Thyroid test / TSH

1. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. (WHO/HTM/TB/2014.11). Geneva, World Health Organization. 2014
Shade cells for the months when the test will not be done
Notation for marking the cells:
0= screen/test not done 1=screen/test done; result pending 2=screen/test done; no SAE
3=screen/test done; SAE detected

16

M24

Annex 5
Alert for serious adverse events to the TB programme
CONFIDENTIAL - To be sent even upon suspicion of a serious adverse event
IS THIS REPORT A NEW EVENT?

1. PATIENT DETAILS
SURNAME
SEX

YES

Male

NO

Female

GIVE DATE WHEN PREVIOUS SAE FORM SENT : (dd/mmm/yyyy)

FIRST NAME
DATE OF BIRTH

DD

MMM

YYYY

age in yrs if
DOB unknown

PREGNANCY

NO

YES

ID NUMBER
ADDRESS

PHONE NO.

SUSPECTED DR

2. SUSPECTED and CONCOMITANT MEDICINE(S)

NAME (Brand name or Generic)

Total daily dose

Date started

Date stopped

Continues

3. DETAILS OF SERIOUS ADVERSE EVENT

DATE EVENT STARTED
DESCRIPTION OF EVENT

WHY IS THE EVENT

CONSIDERED SERIOUS?

4. ACTION TAKEN

Medicine withdrawn

Dose increased

Dose reduced

Dose not changed

Unknown

DATE EVENT STOPPED

Death
Life-threatening event (specify.)
Hospitalization or prolongation of hospitalization
Persistent or significant disability (specify)
Congenital anomaly
Other (specify)
5. OUTCOME OF SERIOUS ADVERSE EVENT
Recovered / resolved
Recovering / resolving
Recovered with sequelae
Not recovered / not resolved
Died
Unknown

6. REPORTER
NAME
FACILITY/CLINIC
ADDRESS

POSITION

E-MAIL

PHONE NO.
DATE SENT

SIGNATURE

17

DD

MMM

YYYY

Explanatory Note
TO BE ADAPTED ACCORDING TO THE LOCAL SITUATION

This form is intended for the Core Package of active tuberculosis drug-safety monitoring and
management (aDSM). For more details please refer to other documents on aDSM. The
spontaneous reporting form in use by the national pharmacovigilance authorities may be
adapted to provide for the purposes of alerting the TB programme of SAEs and avoiding
parallel reporting structures.
The completed form can be sent electronically, via email or fax to <address> and the
responsible authority alerted by phone
The report should be sent within <number> hours after it is detected, even upon suspicion
of seriousness
The report should be sent even if not all details are available and regardless of certainty of
association with any particular medicine. The essential details are the identifiers of the
patient and the reporter; the name of the suspected medicine(s); and basic details on the
serious adverse event
If the report relates to a previously notified event indicate this under section 3; if more than
one serious adverse event occur in the same individual, send separate forms for each event
All health care professionals are encouraged to report. Patients and relatives may also
report
Upon receipt of the information the responsible authority will review the information and
contact the reporter and/or facility for more details. All information, including identity of
the patient and reporter, will be handled in strict confidence. Apart from action to protect
public health, anonymised statistics from these reports will be used to improve drug-safety
When reporting please use DD MMM YYYY format to report dates. In the DESCRIPTION OF
EVENT provide a single diagnosis and include anatomical location if applicable. If diagnosis is
unknown, describe clinical picture.

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References
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